C5aR1-positive adipocytes mediate non-shivering thermogenesis in neonatal mice

Huan-Yu Wang; Xue-Min Peng; Min Yang; Ying Weng; Xi Yang; Di Zhan; Qin Ning; Xiao-Ping Luo; Yong Chen

doi:10.1016/j.isci.2024.111261

C5aR1-positive adipocytes mediate non-shivering thermogenesis in neonatal mice

iScience. 2024 Oct 28;27(12):111261. doi: 10.1016/j.isci.2024.111261. eCollection 2024 Dec 20.

Authors

Huan-Yu Wang^{1

2

3}, Xue-Min Peng^{3

4}, Min Yang^{3

4}, Ying Weng^{1

2}, Xi Yang^{1

2}, Di Zhan^{1

2}, Qin Ning⁵, Xiao-Ping Luo^{1

2}, Yong Chen^{3

4}

Affiliations

¹ Department of Pediatrics, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan 430030, China.
² Hubei Key Laboratory of Pediatric Genetic Metabolic and Endocrine Rare Diseases, Wuhan 430030, China.
³ Research Group of Endocrinology & Metabolism, Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
⁴ Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan 430030, China.
⁵ Department and Institute of Infectious Disease, Tongji Hospital, Tongji Medical College and State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, Huazhong University of Science and Technology, Wuhan 430030, China.

Abstract

Brown adipose tissue (BAT) plays an important role in maintaining body temperature in newborn mammals; however, its mechanisms remain poorly understood. Here, we report the identification of a special population of brown adipose tissue-derived stromal cells (ASCs) in neonatal mice that highly express CD45 and can be differentiated into adipocytes with lower thermogenic ability. These CD45⁺ adipocytes also characteristically contained complement C5a receptor 1(C5aR1) on the cell membrane. C5ar1 deficiency in BAT resulted in an apparent immaturity of adipocytes and cold intolerance in neonatal mice. Mechanistically, loss of C5aR1 in these CD45⁺ brown adipocytes caused an increase in the secretion of plate factor four (PF4) from these cells, suppressing the maturity of neighboring brown adipocytes. Overall, our results indicated that the accumulation of C5aR1 positive brown adipocyte in neonatal BAT is essential for thermoregulation in newborn mice, which unveiled the regulatory mechanism of BAT-mediated thermogenesis in newborns.

Keywords: biochemical mechanism; biochemistry; biological sciences; natural sciences.